Collagen-induced arthritis development requires αβ T cells but not γδ T cells:: studies with T cell-deficient (TCR mutant) mice

Collagen type II (CII)-induced arthritis (CIA) in mice is a model for rheumatoid arthritis (RA) in which the role of T lymphocytes remains controversial. To clarify this, we have bred a targeted gene deletion of TCR beta or delta loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCR beta(-/-) mice lacked alpha beta T cells, which was compensated by an expansion of a cells, gamma delta T cells and NK cells. The beta(-/-) mice, but not control beta(+/-) littermates, were completely resistant to CIA. The production of anti-CII IgG antibodies was also abolished in beta(-/-) mice, revealing a strict ap T cell dependency. In contrast, beta(-/-) mice produced reduced, but significant, anti-CII IgM titers after immunization with either CII or ovalbumin, indicating a multispecificity for these ap T cell-independent IgM antibodies. The TCR delta(-/-) mice lacked gamma delta T cells but had no other significant changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-gamma) in delta(-/-) mice, quantified by flow cytometry staining of mitogen-stimulated lymphocytes, was indistinguishable from normal mice, Likewise, no statistically significant differences were observed in CIA between mice lacking gamma delta T cells and control littermates, considering arthritis incidence, day of disease onset, maximum arthritic score, anti-CII IgG titers and disease course. We conclude that alpha beta T cells are necessary for CIA development and for an IgG response towards CII, whereas gamma delta T cells are neither necessary nor sufficient for development of CIA.